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Pediatric Caroli Disease

  • Author: Mutaz I Sultan, MBChB, MD; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Jul 11, 2016
 

Background

Caroli disease and Caroli syndrome are rare congenital disorders of the intrahepatic bile ducts. They are both characterized by dilatation of the intrahepatic biliary tree. The term Caroli disease is applied if the disease is limited to ectasia or segmental dilatation of the larger intrahepatic ducts. This form is less common than Caroli syndrome, in which malformations of small bile ducts and congenital hepatic fibrosis are also present. This process can be either diffuse or segmental and may be limited to one lobe of the liver, more commonly the left lobe.

Caroli disease is sporadic, whereas Caroli syndrome is generally inherited in an autosomal recessive manner. As with congenital hepatic fibrosis, Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). A rare association with autosomal dominant polycystic kidney disease (ADPKD) has also been reported. See the image below.

Hepatic ultrasonogram of a neonate with Caroli dis Hepatic ultrasonogram of a neonate with Caroli disease. Multiple dilated intrahepatic bile ducts are present. Courtesy of Richard Bellah, MD, The Children's Hospital of Philadelphia.
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Pathophysiology

The precursor of the intrahepatic biliary tree is a sheath of cells surrounding the portal vein branches, known as the ductal plate (DP). The DP first arises from hepatocyte precursors surrounding hilar portal vein vessels at 8 weeks' gestation, and more peripheral regions of the DP develop sequentially. During the remainder of gestation, a process of DP remodeling occurs, during which 1-2 ductules form at points along the circumference of the DP that connect to the intrahepatic biliary tree; the remaining regions of the DP are lost, most likely through apoptosis. Caroli syndrome belongs to a subcategory of diseases thought to originate from DP malformation.

In Caroli disease, abnormalities of the bile duct occur at the level of the large intrahepatic ducts (ie, left and right hepatic ducts, segmental ducts), resulting in dilatation and ectasia. Resulting biliary stasis may lead to cholelithiasis, cholangitis, and sepsis, as well as an increased risk of cholangiocarcinoma.[1] . Because reports have described cases limited to the left lobe of the liver, some have described Caroli disease as either localized or diffuse. 

In Caroli syndrome, DP malformation is present at the level of the smallest portal tracts and is associated with varying degrees of portal fibrosis. These findings are typical of congenital hepatic fibrosis; therefore, Caroli syndrome is thought to belong in the same spectrum of disease as congenital hepatic fibrosis and ARPKD.

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Epidemiology

Frequency

United States

Caroli disease and Caroli syndrome are very rare, with an estimated incidence of less than 1 case per 100,000 population. Caroli syndrome (ectasia of the large and small bile ducts with congenital hepatic fibrosis) is more common than Caroli disease (ectasia of only the large bile ducts).

The incidence of ARPKD/congenital hepatic fibrosis is approximately 1:20,000 live births.[2]

Mortality/Morbidity

Patients with Caroli disease or Caroli syndrome may have recurrent episodes of cholangitis and are also at risk for associated bacteremia and sepsis. Patients with Caroli syndrome or Caroli disease may have cholangitis and may also have complications of portal hypertension as is observed in congenital hepatic fibrosis. Caroli syndrome is associated with ARPKD, and patients may have various degrees of renal cysts, interstitial fibrosis, and renal failure. Both Caroli disease and Caroli syndrome are associated with a risk of cholangiocarcinoma at a rate of 100 times that of the general population.

Sex

Symptoms of Caroli disease or syndrome are more common in female patients than in male patients.

Age

Age at presentation varies and patients may present as neonates or as adults. Cases detected in utero based on ultrasonographic findings have been reported.

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Contributor Information and Disclosures
Author

Mutaz I Sultan, MBChB, MD Assistant Professor of Pediatrics, Al-Quds University Medical College; Pediatric Gastroenterologist and Hepatologist, Division of Pediatrics, Makassed Hospital, Palestine

Mutaz I Sultan, MBChB, MD is a member of the following medical societies: American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Carmen Cuffari, MD Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching.

Additional Contributors

Robert Baldassano, MD Director, Center for Pediatric Inflammatory Bowel Disease, Children's Hospital of Philadelphia; Professor, Department of Pediatrics, Division of Gastroenterology and Nutrition, University of Pennsylvania School of Medicine

Robert Baldassano, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Received consulting fee from Abbott, Inc for consulting.

David A Piccoli, MD Chief of Pediatric Gastroenterology, Hepatology and Nutrition, The Children's Hospital of Philadelphia; Professor, University of Pennsylvania School of Medicine

David A Piccoli, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Joshua R Friedman, MD, PhD Adjunct Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Joshua R Friedman, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Study of Liver Diseases, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Received salary from Johnson & Johnson for employment.

Melissa Kennedy, MD Attending Physician, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia

Melissa Kennedy, MD is a member of the following medical societies: American Academy of Pediatrics, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

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Hepatic ultrasonogram of a neonate with Caroli disease. Multiple dilated intrahepatic bile ducts are present. Courtesy of Richard Bellah, MD, The Children's Hospital of Philadelphia.
 
 
 
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